Polymers Strive for Accuracy: From Sequence-Defined Polymers to mRNA Vaccines against COVID-19 and Polymers in Nucleic Acid Therapeutics

Abstract

Unquestionably, polymers have influenced the world over the past 100 years. They are now more crucial than ever since the COVID-19 pandemic outbreak. The pandemic paved the way for certain polymers to be in the spotlight, namely sequencedefined polymers such as messenger ribonucleic acid (mRNA), which was the first type of vaccine to be authorized in the U.S. and Europe to protect against the SARS-CoV-2 virus. This rise of mRNA will probably influence scientific research concerning nucleic acids in general and RNA therapeutics in specific. In this Perspective, we highlight the recent trends in sequence-controlled and sequence-defined polymers. Then we discuss mRNA vaccines as an example to illustrate the need of ultimate sequence control to achieve complex functions such as specific activation of the immune system. We briefly present how mRNA vaccines are produced, the importance of modified nucleotides, the characteristic features, and the advantages and challenges associated with this class of vaccines. Finally, we discuss the chances and opportunities for polymer chemistry to provide solutions and contribute to the future progress of RNA-based therapeutics. We highlight two particular roles of polymers in this context. One represents conjugation of polymers to nucleic acids to form biohybrids. The other is concerned with advanced polymer-based carrier systems for nucleic acids. We believe that polymers can help to address present problems of RNA-based therapeutic technologies and impact the field beyond the COVID-19 pandemic.

Structure‐Based Varieties of Polymeric Nanocarriers and Influences of Their Physicochemical Properties on Drug Delivery Profiles

“…Nucleic acids, such as, DNA, RNA, etc., encoding viral antigens can be delivered by encapsulating them within polymeric nanovesicles which also contributes to their protection from easy degradation often caused by RNases. [ 187 , 188 ] These pioneering studies have demonstrated that the nanovesicular PNCs have the advantages of biocompatibility and biodegradability, size tuning, co‐loading of adjuvants and active agents, colloidal stability, stimuli‐responsive properties, and antigen functionality. Thus, polymeric nanovesicles are one of the potential multi‐stimuli responsive multi‐drug delivery nanocarrier which can become a prominent candidate to advance vaccine research and provide solution to the ongoing pandemic and beyond.…”

mRNA therapeutics for disease therapy: principles, delivery, and clinical translation

“…The most significant advantage over LNP polymer nanoparticles is that they are easy to synthesize and can be modified by changing the polymer structure to achieve the goal of improved properties. 113 The following is a survey of the latest PNP research progress.…”

The Delivery of mRNA Vaccines for Therapeutics

“…Polymer materials for the delivery of mRNA vaccines have been proven to be efficient in preclinical studies [ 95 ]. However, new functional polymers, with improved biodegradability and delivery efficacy, are desirable before the translation of polymer-based mRNA vaccines in the clinic.…”